Plasticity of BRCA2 Function in Homologous Recombination: Genetic Interactions of the PALB2 and DNA Binding Domains
A. Tr-BRCA2 domain structures. All Tr-BRCA2 peptides are deleted for C-terminal BRC repeats and the BRCA2 DBD at the indicated residues. TrBRC3 and TrBRC5 are additionally deleted for the Cter. TrBRC5-Cter corresponds to a BRCA2 peptide expressed in a PARP inhibitor-resistant revertant of Capan-1 cells (PIR2; ). B. TrBRC-Cter peptides are functional for HR whereas TrBRC peptides are not. The RAD51 binding site at S3291 contributes to HR activity but is not the sole determinant. P≤0.0001 for TrBRC-Cter compared with the respective no Cter or S3291-mutated Cter. C. Disruption of PALB2-binding by W31C mutation (right) is associated with impaired TrBRC5-Cter HR activity (left). P = ≤0.0001 for TrBRC5-Cter compared with the W31C mutation.